Hydrochloric Acid → ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate

HRID 50002Notes

Reaction equation

HRID 50002 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[CH2:11]([O:13][C:14]([C:16]1[C:20]([CH3:21])=[CH:19][NH:18][C:17]=1[CH3:22])=[O:15])[CH3:12].Cl>ClCCl>[CH2:11]([O:13][C:14]([C:16]1[C:20]([CH3:21])=[C:19]([CH:3]=[O:4])[NH:18][C:17]=1[CH3:22])=[O:15])[CH3:12]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 137481Ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate

Product 1

HCID 137485ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

Dimethylformamide (322 g) and dichloromethane (3700 mL) were cooled in an ice bath to 4° C. and phosphorus oxychloride (684 g) was added with stirring. Solid 2,4-dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester (670 g) was slowly added in aliquots over 15 minutes. The maximum temperature reached was 18° C. The mixture was heated to reflux for one hour, cooled to 10° C. in an ice bath and 1.6 L of ice water was rapidly added with vigorous stirring. The temperature increased to 15° C. 10 N Hydrochloric acid (1.6 L) was added with vigorous stirring. The temperature increased to 22° C. The mixture was allowed to stand for 30 minutes and the layers allowed to separate. The temperature reached a maximum of 40° C. The aqueous layer was adjusted to pH 12-13 with 10 N potassium hydroxide (3.8 L) at a rate that allowed the temperature to reach and remain at 55° C. during the addition. After the addition was complete the mixture was cooled to 10° C. and stirred for 1 hour. The solid was collected by vacuum filtration and washed four times with water to give 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester (778 g, 100% yield) as a yellow solid. 1H-NMR (DMSO-d6) δ1.25 (t, 3H, CH3), 2.44, 2.48 (2×s, 2×3H, 2×CH3), 4.16 (q, 2H, CH2), 9.59 (s, 1H, CHO), 12.15 (br s, 1H, NH). MS m/z 195 [M+1].

Workup

  1. customreached was 18° C
  2. temperatureThe mixture was heated
  3. temperatureto reflux for one hour
  4. temperatureThe temperature increased to 15° C
  5. temperatureThe temperature increased to 22° C
  6. customto separate
  7. customa maximum of 40° C
  8. additionremain at 55° C. during the addition
  9. additionAfter the addition
  10. temperaturewas cooled to 10° C.
  11. stirringstirred for 1 hour
  12. filtrationThe solid was collected by vacuum filtration
  13. washwashed four times with water

Sources & evidence

ORD record
ord-a5ffa77d1a2b4ccf8ea881ed5df3f7b2
Source dataset
uspto-grants-2004_03
Patent number
US06710067B2

Reaction notes

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